DESCRIPTION: The interval between vaccination and development of protective immunity is a crucial period for judging efficacy of a vaccine against pathogenic primate lentiviruses. During this period, vaccinees are susceptible to infection with pathogenic virus and the replicating vaccine strain can revert to virulence, recombine with pathogenic virus, or mediate oncologic transformation by integration into the host genome. It is important to understand the mechanism(s) responsible for protective immunity that are elicited by vaccination with a live, non-pathogenic primate lentivirus. This application proposes to test the hypothesis that extended intervals (six months to one year) are required for non-human primates immunized with a live-attenuated primate lentivirus to develop protective immunity against mucosal challenge with a homologous pathogenic virus. To enhance replication of attenuated a novel SHIV 89.6, the investigator proposes to use cyclosporin A immunosuppression. Correlates of protective immunity will be evaluated in parallel with virologic studies. The long term goal is the accelerate the development of protective immunity against pathogenic virus challenge; to accomplish this goal the investigator proposes to engineer a recombinant SHIV virus that replicates slowly but attracts large numbers of lymphocytes by expressing the rhesus T-cell specific chemokine, Lymphotactin, in place of the viral nef gene. The investigator hypothesizes that immunizing rhesus macaques with this Lymphotactin-recombinant SHIV may shorten the time required for protective immunity by recruiting more T-cells to sites of virus replication.